11-2164266-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000360.4(TH):c.1461C>T(p.Asp487=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000445 in 1,346,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: TH NM_000360.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.120

Genes affected

TH (HGNC:11782): (tyrosine hydroxylase) The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-2164266-G-A is Benign according to our data. Variant chr11-2164266-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1155042.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TH	NM_000360.4	c.1461C>T	p.Asp487=	synonymous_variant	13/13	ENST00000352909.8
TH	NM_199292.3	c.1554C>T	p.Asp518=	synonymous_variant	14/14
TH	NM_199293.3	c.1542C>T	p.Asp514=	synonymous_variant	14/14
TH	XM_011520335.3	c.1473C>T	p.Asp491=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TH	ENST00000352909.8	c.1461C>T	p.Asp487=	synonymous_variant	13/13	1	NM_000360.4	P1
TH	ENST00000381178.5	c.1554C>T	p.Asp518=	synonymous_variant	14/14	1
TH	ENST00000381175.5	c.1542C>T	p.Asp514=	synonymous_variant	14/14	1
TH	ENST00000333684.9	c.1179C>T	p.Asp393=	synonymous_variant	11/11	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1346990 Hom.: 0 Cov.: 31 AF XY: 0.00000454 AC XY: 3 AN XY: 660150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000569

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive DOPA responsive dystonia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 22, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.4
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-2185496;